The most recent addition to our laboratories at UCLA, the Sahin-Toth Laboratory focuses on hereditary chronic pancreatitis, a major risk factor for pancreatic cancer. Dr. Miklos Sahin-Toth joined UCLA to work in partnership with Dr. Guido Eibl in our Translational Laboratory to better understand how genetics, obesity, diet, and inflammation contribute to pancreatic cancer acceleration.
Dr. Sahin-Toth and his researchers continue to publish extensively in renowned journals, present at conferences around the world and receive NIH funding. With additional publications forthcoming and grant proposals under consideration, we look forward to sharing updates from Dr. Sahin-Toth and his lab in the near future.
Publications from the Sahin-Toth Laboratory in 2022
1. Chronic progression of cerulein-induced acute pancreatitis in trypsinogen mutant mice. Pancreatology 2022, 22:248-257. PMC8941852
Jancsó Z, Sahin-Tóth M.
This is an important follow-up study on our high-impact 2020 Gastroenterology paper that described increased severity of acute pancreatitis in mice carrying a trypsinogen mutation. Here we demonstrated that this trypsinogen mutation also sensitizes mice to chronic pancreatitis. Pancreatology is the official journal of the International Association of Pancreatology and the European Pancreatic Club.
2. Misfolding-induced chronic pancreatitis in CPA1 N256K mutant mice is unaffected by global deletion of Ddit3/Chop. Scientific Reports 2022, 12:6357. PMC9012826
Németh BC, Demcsák A, Geisz A, Sahin-Tóth M.
In our seminal 2019 Gut paper, we found high levels of the signaling molecule CHOP in mice with chronic pancreatitis due to a mutation in the digestive enzyme carboxypeptidase A1 (CPA1). In this follow-up study, we demonstrated that CHOP plays no role in disease initiation or progression. In other words, CHOP is a marker rather than a driver of chronic pancreatitis. The Scientific Reports is an open-access journal publishing original research from all areas of life sciences. It is part of the prestigious Nature Research journal family.
3. Modelling chronic pancreatitis as a complex genetic disease in mice. Gut 2022 May 16. Epub ahead of print. PMC9666703
Jancsó Z, Demcsák A, Sahin-Tóth M.
Chronic pancreatitis is a complex genetic disease, and patients often carry multiple genetic variants. Here we crossed mouse strains with different pancreatitis-associated gene variants to study their combined effect. This remarkable study showed that mice with single genetic changes showed no pancreas disease; however, mice with both gene variants developed severe chronic pancreatitis. Gut is a preeminent journal in the gastroenterological sciences, published in Europe by BMJ.
4. Variants in the pancreatic CUB and zona pellucida-like domains 1 (CUZD1) gene in early-onset chronic pancreatitis – A possible new susceptibility gene. Pancreatology 2022, 22:564-571. PMC9250292
Rygiel AM, Unger LS, Sörgel FL, Masson E, Matsumoto R, Ewers M, Chen JM, Bugert P, Buscail L, Gambin T, Oracz G, Winiewska-Szajewska M, Mianowska A, Poznanski J, Kosińska J, Stawinski P, Płoski R, Koziel D, Gluszek S, Laumen H, Lindgren F, Löhr JM, Orekhova A, Rebours V, Rosendahl J, Párniczky A, Hegyi P, Sasaki A, Kataoka F, Tanaka Y, Hamada S, Sahin-Tóth M, Hegyi E, Férec C, Masamune A, Witt H.
Discovery of new gene variants that increase risk for chronic pancreatitis is an ongoing collaborative effort. In this paper, we contributed biochemical experiments to demonstrate that mutations in the CUZD1 gene may act as risk factors for chronic pancreatitis. CUZD1 is an abundant protein in the pancreas with unclear function. Pancreatology is the official journal of the International Association of Pancreatology and the European Pancreatic Club.
5. Risk of chronic pancreatitis in carriers of loss-of-function CTRC variants: A meta-analysis. PLoS One 2022, 17:e0268859. PMC9122191
Takáts A, Berke G, Gede N, Németh BC, Witt H, Głuszek S, Rygiel AM, Hegyi P, Sahin-Tóth M, Hegyi E.
Meta-analysis of published studies is an important tool to define the extent of risk associated with various genetic variants in chronic pancreatitis. In this collaborative paper, we analyzed variants in the chymotrypsin C (CTRC) gene, which encodes a pancreatic digestive protease that protects the pancreas against harmful trypsin activity and pancreatitis. The journal PLoS One is published by the Public Library of Science as a peer-reviewed, open-access forum for a broad spectrum of scientific results.
6. Rate of autoactivation determines pancreatitis phenotype in trypsinogen mutant mice. Gastroenterology 2022, 163:761-763. PMC9398983
Demcsák A, Sahin-Tóth M.
Our flagship paper for the year! Here we demonstrated that the propensity of mutant trypsinogen to become active determines the severity of pancreatitis in mice, and by extension, in humans. Gastroenterology is the official journal of the American Gastroenterological Association (AGA), and the most prominent US publication in the gastroenterological sciences.
7. Loss-of-function variant in chymotrypsin like elastase 3B (CELA3B) is associated with non-alcoholic chronic pancreatitis. Pancreatology 2022, 22:713-718. PMC9474678
Tóth A, Demcsák A, Zankl F, Oracz G, Unger LS, Bugert P, Laumen H, Párniczky A, Hegyi P, Rosendahl J, Gambin T, Płoski R, Koziel D, Gluszek S, Lindgren F, Löhr JM, Sahin-Tóth M, Witt H, Rygiel AM, Ewers M, Hegyi E.
Discovery of new gene variants that increase risk for chronic pancreatitis is an ongoing collaborative effort. In this paper, we contributed biochemical experiments to demonstrate that a mutation in the CELA3B gene acts as a risk factor for chronic pancreatitis. The CELA3B gene encodes a pancreatic digestive protease called elastase 3B. Pancreatology is the official journal of the International Association of Pancreatology and the European Pancreatic Club.
8. Hereditary pancreatitis-25 years of an evolving paradigm: Frank Brooks Memorial Lecture 2021. Pancreas 2022, 51:297-301. PMC9348779
On November 4, 2021, Dr. Sahin-Tóth had the special honor of delivering the Frank Brooks Memorial Lecture at the Annual Meeting of the American Pancreatic Association. This article summarizes key points of the lecture, and the milestones of the past 25 years spent on researching hereditary pancreatitis. Pancreas is the official journal of the American Pancreatic Association (APA).
9. Arg236 in human chymotrypsin B2 (CTRB2) is a key determinant of high enzyme activity, trypsinogen degradation capacity, and protection against pancreatitis. Biochimica et Biophysica Acta – Proteins and Proteomics 2022, 1870:140831. PMC9426946.
Németh BZ, Demcsák A, Micsonai A, Kiss B, Schlosser G, Geisz A, Hegyi E, Sahin-Tóth M, Pál G.
As part of a large international collaboration, previously we identified a common genetic change in the chymotrypsin B1-B2 genes (CTRB1-CTRB2) that protects against chronic pancreatitis (Gut 2018). In this elegant follow-up study, we collaborated with Dr. Gabor Pal’s group to provide biochemical data that further clarified the mechanism by which chymotrypsins protect against pancreatitis. Biochimica et Biophysica Acta is one of the oldest scientific journals in the field of biochemistry, published by Elsevier.
10. Preclinical testing of dabigatran in trypsin-dependent pancreatitis. Journal of Clinical Investigation Insight 2022, 7:e161145. PMC9675574
Pesei ZG, Jancsó Z, Demcsák A, Németh BC, Vajda S, Sahin-Tóth M.
A compelling story offering hope for the development of a drug treatment for chronic pancreatitis! Here we used mice with a trypsinogen mutation to demonstrate that the anticoagulant drug dabigatran etexilate (brand name Pradaxa) had good therapeutic efficacy in pancreatitis. JCI Insight is the open-access sister journal of the distinguished Journal of Clinical Investigation (JCI), which publishes high-quality studies that provide meaningful contributions to the understanding of the biology and treatment of disease.
11. Bicarbonate defective CFTR variants increase risk for chronic pancreatitis: A meta-analysis. PLoS One 2022, 17:e0276397. PMC9584382.
Berke G, Gede N, Szadai L, Ocskay K, Hegyi P, Sahin-Tóth M, Hegyi E.
Meta-analysis of published studies is an important tool to define the extent of risk associated with various genetic variants in chronic pancreatitis. In this collaborative study, we analyzed the association of variants in the cystic fibrosis transmembrane conductance regulator (CFTR) gene and chronic pancreatitis. The journal PLoS One is published by the Public Library of Science as a peer-reviewed, open-access forum for a broad spectrum of scientific results.
12. Novel p.G250A mutation associated with chronic pancreatitis highlights misfolding-prone region in carboxypeptidase A1 (CPA1). International Journal of Molecular Sciences 2022, 23:15463. PMC9779553
Sándor M, Thiel FG, Schmid M, Demcsák A, Morales Granda NC, Németh BC, Vajda S, Hoerning A, Sahin-Tóth M.
Characterization of novel gene mutations found in patients with chronic pancreatitis is an ongoing project in our laboratory. Here we described functional properties of a newly identified gene variant in the digestive enzyme carboxypeptidase A1 (CPA1). Mutations in this enzyme have been known to cause hereditary pancreatitis in humans. The International Journal of Molecular Sciences is an open-access journal providing an advanced forum for a large variety of research projects, including biochemistry.